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PROTECT: What Have We Learned. Lesson 2: TMPG is associated with clinical and biomarker outcomes following PCI. Association of Post PCI TMPG 3 with Adverse Outcomes. TMPG 0,1,2 n=327 TMPG 3 n=411. p=0.005. p=0.011. p=0.084. %.
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PROTECT: What Have We Learned Lesson 2: TMPG is associated with clinical and biomarker outcomes following PCI
Association of Post PCI TMPG 3 with Adverse Outcomes TMPG 0,1,2 n=327 TMPG 3 n=411 p=0.005 p=0.011 p=0.084 %
Association of CFR and Post-PCI TMPG with Clinical, Biomarker and Holter Outcomes Coronary Flow Reserve (CFR) TMPG 0,1,2 vs TMPG 3
Multivariate Model Of Death / MI / Ischemia on HolterThrough 48 Hours • Odds ratio of death / MI / Ischemia on Holter 1.7 (95% CI 1.10 - 2.57, p=0.017) for closed muscle (TMPG 0,1,2) when adjusting for post PCI CFR (p=0.27, NS)
Lesson 3: What is the most powerful predictor of the baseline troponin before PCI?
Impaired Myocardial Perfusion on the Diagnostic Cath Circulation 2002;106:202-207
Association of Baseline Troponin I with the Pre-PCI TMPG Odds of leaving cath lab with an open muscle were 6.2 times higher if you arrive to lab with an open muscle (p<0.001) Median: 0.36 Mean 3.28 + 7.07 p<0.0001 Troponin I Median: 0.07 Mean 1.47 + 3.86 N=289 N=362
PROTECT: What Have We Learned Lesson 4: The peak and the rise in markers of myonecrosis is related not only to myocardial perfusion after PCI, but also to the myocardial perfusion before the PCI
Myocardial Perfusion Before and After PCI & Its Relationship to Rise in Markers of Myonecrosis Post PCI by Treatment Group Open Myocardium p=NS p=NS Open Myocardium TMPG 3 Closed Myocardium p=NS p=NS p=0.009 p=0.04 Open Myocardium Closed Myocardium TMPG 0/1/2 p=NS p=NS Closed Myocardium Rise in Tn I Post PCI Rise in CKMB Post PCI
Univariate Correlates of Post-PCI TMPG 3 Non-significant covariates: age (p=0.49); gender (p=0.42); race (p=0.51); prior CHF (p=0.67);prior MI (p=0.69);history of angina (p=0.46);prior stenosis > 50% (p=0.98);prior PCI (p=0.26);history of CABG (p=0.35);known EF <50% (p=0.70);history of HTN (p=0.79);family history (p=0.98);history of diabetes (p=0.25);diagnosis of UA vs NSTEMI (p=0.27);ST deviation of 0.5 – 0.9 mm (p=0.94);ST deviation of > 1.0 mm (p=0.75);systolic BP at randomization (p=0.64);diastolic BP (p=0.27);heart rate (p=0.92);weight (p=0.83);prior ASA use (p=0.95);prior beta blocker use (p=0.70);prior ACE use (p=0.93);prior Ca channel blocker use (p=0.37);prior ARB (p=0.91);prior nitrates (p=0.50);pre-PCI TIMI Flow Grade (p=0.84).
Prior Studies Linking GP IIbIIIa Inhibition and Improved Myocardial Perfusion INTEGRITI ESPRIT TACTICS Rate of Increase in DSA Brightness (Gray /sec) Longer / Earlier Upstream GPIIbIIIa Inhibition Improves Rate of TMPG3 Index of Absolute Number of 2b3a Receptors Unoccupied 79.6 + 58.4K Median 67.8K 7.30 + 8.13 p = 0.030 P=0.05 Count (in thousands) 51.2 24.8K Median 54.0K p = 0.018 3.97 + 2.46 % TMPG 3 Gray per sec N = 253 n=26 N = 253 N=27 N=18 n=21 “Upstream” Duration (> median) Post PCI TMPG 0/1 Post PCI TMPG 2/3 Heparin Heparin + Eptifibatide Gibson CM et al, AJC 2001;87(11):1293-5. Gibson CM et al, Circulation. 2004;110:679-684. Gibson. Am J Cardiol. 2004; 94:492-4
Prior Studies Linking GP IIbIIIa Inhibition and Improved Myocardial Perfusion GP IIbIIIa Inhibition was Associated with a More Rapid Rate of Rise in Myocardial Contrast ECHO (MCE) Intensity Following Reperfusion in Animal Model Kunichika, … Demaria A et al, J Am Coll Cardiol 2004;43:276–83
PROTECT: What Have We Learned Lesson 5: Abnormal myocardial perfusion post-PCI is related to ischemia post-PCI, and Eptifibatide significantly reduces the duration of ischemia compared to Bivalirudin when it does occur
Association of Post PCI TMPG 3 with Holter Findings TMPG 0,1,2 n=327 TMPG 3 n=411 p=0.011 p=0.034 % Ischemia Duration (min) TMPG 0,1,2 TMPG 3 TMPG 0,1,2 TMPG 3
CAPTURE & PROTECT Trials Holter Substudies CAPTURE PROTECT P=0.013 p=0.10 Total Duration ST Depression Per Patient (min) Heparin Abciximab Bivalirudin Integrilin + UFH or Enox Klootwijk, Circulation 1998;98:1358-1364.